Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Tipifarnib in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome in Complete Remission

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	JHOC-J0252 MSGCC-0150, NCI-5689, NCT00045396, 5689

Objectives

1. Determine the duration of disease-free survival and overall survival of patients with poor-risk acute myeloid leukemia or high-risk myelodysplastic syndromes in early first complete remission treated with tipifarnib.
2. Determine the tolerability and toxic effects of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed diagnosis of 1 of the following:
  • Poor-risk acute myeloid leukemia (AML), defined as any of the following:
    • Antecedent hematologic disorder
    • AML arising from myelodysplastic syndromes (MDS)
    • Therapy-related AML
    • 60 years of age or over (in absence of favorable cytogenetics)
    • Adverse cytogenetics (e.g., -5/5q, -7/7q, 20q-, or 11q23 abnormalities or complex karyotype)
    • Hyperleukocytosis at diagnosis (e.g., blasts at least 50,000/mm³ in absence of favorable cytogenetics)
    • No acute promyelocytic leukemia (FAB M3 subtype)
  
  
  
  • High-risk myelodysplastic syndromes (MDS), defined as any of the following:
    • Chronic myelomonocytic leukemia with more than 5% marrow blasts
    • Therapy-related MDS
    • Refractory anemia with excess blasts (RAEB) with IPSS score at least 1.5
    • RAEB in transformation with IPSS score at least 1.5
  
  
  



• In early first complete remission after completing induction and consolidation chemotherapy
  • No more than 21-35 days since hospital discharge after marrow recovery from consolidation therapy
  • No more than 120 days since initiation of the final course of consolidation therapy



• No presence of residual AML (more than 5% marrow blasts) or MDS by morphology, flow cytometry, and/or cytogenetics



• No active CNS leukemia



• No presence of (8;21) translocation or inversion 16 genotype as sole abnormality



• Ineligible for curative allogeneic stem cell transplantation

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• No prior tipifarnib
• No concurrent participation in another phase II or phase III study in which disease-free survival and overall survival are primary endpoints

Patient Characteristics:

Age

• See Disease Characteristics
• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Polymorphonuclear cell count at least 1,000/mm³
• Platelet count at least 30,000/mm³*
• Hemoglobin at least 9 g/dL*
• Hematocrit at least 27%*

 [Note: *Unsupported]

Hepatic

• Bilirubin no greater than 1.5 times normal
• AST and ALT no greater than 2.5 times normal
• Alkaline phosphatase no greater than 2.5 times normal

Renal

• Creatinine no greater than 2.0 mg/dL

  OR

• Creatinine clearance at least 40 mL/min

Cardiovascular

• No disseminated intravascular coagulation
• LVEF at least 25%

Other

• No active uncontrolled infection
• No known allergy to imidazole drugs (e.g., ketoconazole or miconazole)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 14-44 patients will be accrued for this study within 11-15 months.

Outcomes

6-month disease-free survival

Tolerability and toxicity

Outline

This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

Karp JE, Smith BD, Gojo I, et al.: Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features. Clin Cancer Res 14 (10): 3077-82, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Judith Karp, MD, Protocol chair		Ph: 410-502-7726

Registry Information
Official Title		A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)
Trial Start Date		2002-08-21
Registered in ClinicalTrials.gov		NCT00045396
Date Submitted to PDQ		2002-06-28
Information Last Verified		2006-04-08
NCI Grant/Contract Number		CA69854, CA06973

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